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Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells

Overview of attention for article published in Breast Cancer Research, December 2017
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Title
Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells
Published in
Breast Cancer Research, December 2017
DOI 10.1186/s13058-017-0924-4
Pubmed ID
Authors

Asfa Alli-Shaik, Sheena Wee, Lina H. K. Lim, Jayantha Gunaratne

Abstract

Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells. Quantitative phosphoproteomics analysis of mammary gland epithelial cells derived from ANXA1-heterozygous and ANXA1-deficient mice was carried out using stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry. Kinase and signaling changes underlying ANXA1 perturbations were derived by upstream kinase prediction and integrated network analysis of altered proteins and phosphoproteins. We identified a total of 8110 unique phosphorylation sites, of which 582 phosphorylation sites on 372 proteins had ANXA1-responsive changes. A majority of these phosphorylation changes occurred on proteins associated with cytoskeletal reorganization spanning the focal adhesion, stress fibers, and also the microtubule network proposing new roles for ANXA1 in regulating microtubule dynamics. Comparative analysis of regulated global proteome and phosphoproteome highlighted key differences in translational and post-translational effects of ANXA1, and suggested closely coordinated rewiring of the cell adhesion network. Kinase prediction analysis suggested activity modulation of calmodulin-dependent protein kinase II (CAMK2), P21-activated kinase (PAK), extracellular signal-regulated kinase (ERK), and IκB kinase (IKK) upon loss of ANXA1. Integrative analysis revealed regulation of the WNT and Hippo signaling pathways in ANXA1-deficient mammary epithelial cells, wherein there is downregulation of transcriptional effects of TEA domain family (TEAD) suggestive of ANXA1-responsive transcriptional rewiring. The phosphoproteome landscape uncovered several novel perspectives for ANXA1 in mammary gland biology and highlighted its involvement in key signaling pathways modulating cell adhesion and migration that could contribute to breast cancer initiation.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 19%
Student > Master 4 15%
Student > Ph. D. Student 3 12%
Professor > Associate Professor 3 12%
Researcher 3 12%
Other 1 4%
Unknown 7 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 31%
Agricultural and Biological Sciences 3 12%
Engineering 2 8%
Immunology and Microbiology 2 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Other 3 12%
Unknown 7 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2018.
All research outputs
#20,663,600
of 25,382,440 outputs
Outputs from Breast Cancer Research
#1,708
of 2,054 outputs
Outputs of similar age
#338,268
of 443,738 outputs
Outputs of similar age from Breast Cancer Research
#19
of 20 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
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We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.